Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

The role of CELF family in neurodevelopment and neurodevelopmental disorders.

RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1-6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Real-Time Cardiac Abnormality Monitoring and Nursing for Patient using Electrocardiographic Signals.

Introduction Cardiovascular disease care is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. Methods This research reconstructed the vector model for arbitrary leads using the phase space time delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. Result Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. Afterwards, the detail differences of the electrocardiogram signal were amplified using a single-lead three-dimensional model. A cropping algorithm was used to remove waveforms severely interfered by external factors. Then, automatic neural network recognition was used. The automatic network generation model was designed effectively for different data types. The accuracy of patient identification is 98.2%, and the accuracy for healthy patients is 99.2%. Conclusion The elastic wavelet neural network can automatically denoise. Through the three-dimensional model, the detailed changes of electrocardiogram signals of different diseases can be observed. The cropping algorithm effectively identified the interfered and destroyed waveforms. The automatic neural network is capable of carrying out disease type classification and patient identity classification.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Social support predicted subsequent subjective well-being during the COVID-19 pandemic: a prospective study.

BACKGROUND: Subjective well-being (SWB) is associated with social support in cross-sectional studies. However, it remains unclear whether and how social support predicts SWB longitudinally, especially during the COVID-19 contingency. METHODS: By adopting a prospective design, the current work addressed this research question in a sample of 594 participants from the U.K. The data were collected via the online platform, Prolific, at two time points (June, 2020 and August, 2021) with a 14-month interval. Descriptive analysis and a moderated mediation model were conducted to test the proposed hypotheses. RESULTS: Baseline social support was a significant predictor of subjective well-being (SWB) 14 months later, even after controlling for baseline SWB and other covariates such as personality traits. Additionally, affect balance (i.e., the affective component of SWB) fully mediated the link between baseline social support and subsequent life satisfaction (i.e., the cognitive component of SWB). Moreover, household income moderated this relationship, indicating a stronger mediation for individuals with lower monthly household income. CONCLUSION: The present work sheds light on the underlying mechanism and boundary condition of the association between social support and different components of SWB during the COVID-19 pandemic.

Variable Time-Step Physics Engine with Continuous Compliance Contact Model for Optimal Robotic Grinding Trajectory Planning.

In the transition from virtual environments to real-world applications, the role of physics engines is crucial for accurately emulating and representing systems. To address the prevalent issue of inaccurate simulations, this paper introduces a novel physics engine uniquely designed with a compliant contact model designed for robotic grinding. It features continuous and variable time-step simulations, emphasizing accurate contact force calculations during object collision. Firstly, the engine derives dynamic equations considering spring stiffness, damping coefficients, coefficients of restitution, and external forces. This facilitates the effective determination of dynamic parameters such as contact force, acceleration, velocity, and position throughout penetration processes continuously. Secondly, the approach utilizes effective inertia in developing the contact model, which is designed for multi-jointed robots through pose transformation. The proposed physics engine effectively captures energy conversion in scenarios with convex contact surface shapes through the application of spring dampers during collisions. Finally, the reliability of the contact solver in the simulation was verified through bouncing ball experiments and robotic grinding experiments under different coefficients of restitution. These experiments effectively recorded the continuous variations in parameters, such as contact force, verifying the integral stability of the system. In summary, this article advances physics engine technology beyond current geometrically constrained contact solutions, enhancing the accuracy of simulations and modeling in virtual environments. This is particularly significant in scenarios wherein there are constant changes in the outside world, such as robotic grinding tasks.

Prediction of jaw opening function after mandibular reconstruction using subject-specific musculoskeletal modelling.

BACKGROUND: Mandibular reconstruction patients often suffer abnormalities in the mandibular kinematics. In silico simulations, such as musculoskeletal modelling, can be used to predict post-operative mandibular kinematics. It is important to validate the mandibular musculoskeletal model and analyse the factors influencing its accuracy. OBJECTIVES: To investigate the jaw opening-closing movements after mandibular reconstruction, as predicted by the subject-specific musculoskeletal model, and the factors influencing its accuracy. METHODS: Ten mandibular reconstruction patients were enrolled in this study. Cone-beam computed tomography images, mandibular movements, and surface electromyogram signals were recorded preoperatively. A subject-specific mandibular musculoskeletal model was established to predict surgical outcomes using patient-averaged muscle parameter changes as model inputs. Jaw bone geometry was replaced by surgical planning results, and the muscle insertion sites were registered based on the non-rigid iterative closest point method. The predicted jaw kinematic data were validated based on 6-month post-operative measurements. Correlations between the prediction accuracy and patient characteristics (age, pathology and surgical scope) were further analysed. RESULTS: The root mean square error (RMSE) for lower incisor displacement was 31.4%, and the error for peak magnitude of jaw opening was 4.9 mm. Age, post-operative infection and radiotherapy influenced the prediction accuracy. The amount of masseter detachment showed little correlation with jaw opening. CONCLUSION: The mandibular musculoskeletal model successfully predicted short-range jaw opening functions after mandibular reconstruction. It provides a novel surgical planning method to predict the risk of developing trismus.

Evaluation of joint kinematics in patients with condylar reconstruction using mandibular motion simulation based on intraoral scanning registration.

AIM: To summarize the features of condylar kinematics in patients with condylar reconstruction using a mandibular motion simulation method based on intraoral scanning registration. MATERIALS AND METHODS: Patients undergoing unilateral segmental mandibulectomy and autogenous bone reconstruction as well as healthy volunteers were enrolled in the study. Patients were grouped based on whether the condyles were reconstructed. Mandibular movements were recorded using a jaw tracking system, and kinematic models were simulated after registration. The path inclination of the condyle point, margin of border movement, deviation, and chewing cycle were analyzed. A t test and one-way analysis of variance (ANOVA) were carried out. RESULTS: A total of 20 patients, including 6 with condylar reconstruction and 14 with condylar preservation as well as 10 healthy volunteers were included. The patients with condylar reconstruction showed flatter movement paths of the condyle points. The mean inclination angle of the condylar movement paths of the patients with condylar reconstruction (0.57 ± 12.54 degrees) was significantly smaller than that of those with condylar preservation (24.70 ± 3.90 degrees, P = 0.014) during both maximum opening and protrusion (7.04 ± 12.21 degrees and 31.12 ± 6.79 degrees, respectively, P = 0.022). The inclination angle of the condylar movement paths of the healthy volunteers was 16.81 ± 3.97 degrees during maximum opening and 21.54 ± 2.80 degrees during protrusion; no significant difference compared with the patients. The condyles of the affected side tended to deviate laterally in all patients during mouth opening and protrusion. Patients with condylar reconstruction showed more severe symptoms of mouth opening limitation and mandibular movement deviation as well as shorter chewing cycles than patients with condylar preservation. CONCLUSION: Patients with condylar reconstruction showed flatter movement paths of the condyle points, greater lateral motion range, and shorter chewing cycles than those with condylar preservation. The method of mandibular motion simulation based on intraoral scanning registration was feasible to simulate condylar movement.

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme.

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR-RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

Thermomonas mangrovi sp. nov., isolated from soil of a mangrove nature reserve.

A Gram-stain-negative, non-motile, aerobic and ovoid-rod-shaped bacterial strain, designated as 2C3345T, was isolated from soil of a mangrove nature reserve in Shenzhen, PR China and its taxonomic position was investigated. The 16S rRNA gene sequence of strain 2C3345T exhibited the highest similarity value to that of the type strains Thermomonas aquatica NBRC 113114T (98.4 %), Thermomonas carbonis KCTC 42013T (98.1 %), Thermomonas brevis DSM 15422T (98.0 %) and Thermomonas haemolytica DSM 13605T (97.9 %). Strain 2C3345T grew optimally at 28-30 °C, pH 7.0 and without NaCl. The predominant ubiquinone in 2C3345T was identified as Q-8. The major fatty acids of 2C3345T were iso-C15 : 0, iso-C16 : 0 and summed feature 9 (is0-C17:1ω9c and/or 10-methyl C16:0). The major polar lipids of 2C3345T were phosphatidylcholine (PC), phosphatidylglycerol (PG), diphosphatidglycerol (DPG), phosphatidylethanolamine (PE), an unidentified phospholipid, an unidentified aminolipid and two unidentified lipids. The DNA G+C content of strain 2C3345T was 69.9 %. The draft genome sequence of 2C3345T included 2 888 645 bp in total (N50=310 730 bp) with a medium read coverage of 388.6×and 21 scaffolds. In silico DNA-DNA hybridisation with type strains of species of the genus Thermomonas showed 24.4, 22.4, 24.1 and 23.2% relatedness to T. aquatica NBRC 113114T, T. carbonis KCTC 42013T, T. brevis DSM 15422T and T. haemolytica DSM 13605T, respectively. And the average nucleotide identity by blast (ANIb) values between 2C3345T and these four reference strains were 81.9, 80.0, 81.2 and 80.6 %, respectively, lower than the 95-96% threshold value for dividing prokaryotic species. On the basis of its phenotypic, chemotaxonomic, phylogenetic and phylogenomic properties, strain 2C3345T is considered to represent a novel species within the genus Thermomonas, for which the name Thermomonas mangrovi sp. nov. is proposed. The type strain is 2C3345T (=KCTC 92730T =MCCC 1K08335T).

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.

BACKGROUND: Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3-5 CKD. METHODS: In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records. RESULTS: This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups. CONCLUSIONS: Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3-5 helped relieve physical deterioration and increased micronutrient intake after three months. TRIAL REGISTRATION: ClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).

A candidate virulence factor of Eimeria tenella (EtROP30) predicted by virulence enhancement of transgenic Toxoplasma gondii.

Difficulties of in vitro culture and genetic manipulation of Eimeria tenella have hindered the screening of virulence factors in this parasite. In this study, the E. tenella rhoptry protein 30 (EtROP30) was expressed in Toxoplasma gondii (RH∆Ku80-EtROP30), and its effect on the proliferation and virulence of parasites was investigated. The results revealed that the expression of EtROP30 had no impact on the invasion and egress processes. However, the RH∆Ku80-EtROP30 strain formed larger plaques compared to the RH∆Ku80, indicating that the EtROP30 expression promotes T. gondii proliferation. Furthermore, the RH∆Ku80-EtROP30 strain exhibited greater pathogenicity, resulting in earlier mortality and shorter overall survival time compared to RH∆Ku80. These results imply that EtROP30 expression facilitates parasite intracellular proliferation and virulence in mice, suggesting that EtROP30 might be a candidate virulence factor of E. tenella.

TgMORN2, a MORN Family Protein Involved in the Regulation of Endoplasmic Reticulum Stress in Toxoplasma gondii.

MORN proteins play a key role in the cytoskeletal structure of eukaryotes and are essential for the close arrangement of the endoplasmic reticulum and plasma membrane. A gene with nine MORN motifs (TGGT1_292120, named TgMORN2) was identified in the Toxoplasma gondii genome; it was presumed to belong to the MORN protein family and to have the function of forming the cytoskeleton, which affects the survival of T. gondii. However, the genetic deletion of MORN2 did not noticeably affect parasite growth and virulence. Using adjacent protein labeling techniques, we identified a network of TgMORN2 interactions, which mainly included endoplasmic reticulum stress (ER stress)-related proteins. In exploring these data, we found that the pathogenicity of the KO-TgMORN2 strain was significantly reduced in the case of tunicamycin-induced ER stress. Reticulon TgRTN (TGGT1_226430) and tubulin ß-Tubulin were identified as interaction proteins of TgMORN2. Collectively, TgMORN2 plays a role in ER stress, which lays a foundation for further research on the function of the MORN protein in T. gondii.

Giant Mandibular Ameloblastoma with Rare Hypercalcemia: A Case Report and Literature Review.

Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient's poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient's condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.

Epidemiological investigation and reinfection evaluation of Toxoplasma gondii in chickens in Shandong Province, China.

Toxoplasma gondii infects almost all warm-blooded animals, and toxoplasmosis is a common zoonotic parasitic disease worldwide. A nested PCR with high specificity and sensitivity was developed in this study based on the data collected on the infection rate of toxoplasmosis in chickens in Shandong province, and the effect of low temperature on the infectivity of tachyzoites was investigated. The sampling data showed that the total prevalence of T. gondii in Shandong province was 12.3%, and the positive rate varied in different regions, ranging from 6.7% to 21%. Chickens were infected with T. gondii under laboratory conditions, and positive chicken hearts were stored under various cold conditions to infect mice for reinfection evaluation. The results demonstrated that the parasites maintained high infectivity in mice even after 6 h of storage at -20 °C ambient temperature, indicating that short-term cryopreservation is not effective in reducing the risk of T. gondii transmission. These results form the basis for assessing the risk of toxoplasmosis contamination in consumed chicken products and provide information on the prevention of parasite transmission from animals to humans.

Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii.

We had shown in our previous study that TgUrm1 (ubiquitin-related Modifier 1) was involved in the regulation of anti-oxidant stress in Toxoplasma gondii by conjugating with TgAhp1. It is generally believed that Urm1 binds to target proteins through a mechanism involving Uba (ubiquitin-like activator protein). Here, we identified the TgUrm1-exclusive ubiquitin-like activator-TgUba1, which was located in the cytoplasm of Toxoplasma. TgUba1 contained three domains, including the atrophin-1 domain (ANT1), the E1-like domain (AD), and the rhodanese homology domain (RHD). We explored the interaction of TgUba1 with TgUrm1, and the AD domain was essential for the interaction of the two proteins. The TgUba1 knockout and complementary mutants were obtained based on CRISPR/Cas9 gene editing technology. The knockout of TgUba1 attenuated parasite proliferation and virulence in mice, but not invasion and egress processes, revealing the pivotal role played by TgUba1 in T. gondii survival. Meanwhile, the conjugate band of TgUrm1 was significantly reduced under oxidative stress stimulation without TgUba1, indicating that TgUba1 enhanced the targeted conjugation ability of TgUrm1 in response to oxidative stress, especially under diamide (Dia) stimulation. Furthermore, eleven TgUba1-interacting proteins were identified by proximity-based protein labeling techniques, relating them to ubiquitin-like modifications, anti-oxidative stress and metabolic regulation processes. In conclusion, TgUba1 was essential for T. gondii survival and might be a potential ubiquitin-like activator protein for TgUrm1.

Integrative analysis of histomorphology, transcriptome and whole genome resequencing identified DIO2 gene as a crucial gene for the protuberant knob located on forehead in geese.

BACKGROUND: During domestication, remarkable changes in behavior, morphology, physiology and production performance have taken place in farm animals. As one of the most economically important poultry, goose owns a unique appearance characteristic called knob, which is located at the base of the upper bill. However, neither the histomorphology nor the genetic mechanism of the knob phenotype has been revealed in geese. RESULTS: In the present study, integrated radiographic, histological, transcriptomic and genomic analyses revealed the histomorphological characteristics and genetic mechanism of goose knob. The knob skin was developed, and radiographic results demonstrated that the knob bone was obviously protuberant and pneumatized. Histologically, there were major differences in structures in both the knob skin and bone between geese owing knob (namely knob-geese) and those devoid of knob (namely non-knob geese). Through transcriptome analysis, 592 and 952 genes differentially expressed in knob skin and bone, and significantly enriched in PPAR and Calcium pathways in knob skin and bone, respectively, which revealed the molecular mechanisms of histomorphological differences of the knob between knob- and non-knob geese. Furthermore, integrated transcriptomic and genomic analysis contributed to the identification of 17 and 21 candidate genes associated with the knob formation in the skin and bone, respectively. Of them, DIO2 gene could play a pivotal role in determining the knob phenotype in geese. Because a non-synonymous mutation (c.642,923 G > A, P265L) changed DIO2 protein secondary structure in knob geese, and Sanger sequencing further showed that the AA genotype was identified in the population of knob geese, and was prevalent in a crossing population which was artificially selected for 10 generations. CONCLUSIONS: This study was the first to uncover the knob histomorphological characteristics and genetic mechanism in geese, and DIO2 was identified as the crucial gene associated with the knob phenotype. These data not only expand and enrich our knowledge on the molecular mechanisms underlying the formation of head appendages in both mammalian and avian species, but also have important theoretical and practical significance for goose breeding.

L-Arg-Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing.

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H2 O2 generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen (1 O2 ) production. The combination of 1 O2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

Cancer stemness of CD10-positive cells regulated by Hedgehog pathway promotes the resistance to cisplatin in oral squamous cell carcinoma.

OBJECTIVE: To explore the role of CD10 in cisplatin resistance of oral squamous cell carcinoma (OSCC) and its association with the Hedgehog (Hh) signaling pathway and cancer stem cells (CSCs). METHODS: The correlation between cell viability and CD10 expression was analyzed in different OSCC cell lines after the cisplatin treatment. Genes related to chemotherapy resistance, cancer stem cells and the epithelial-mesenchymal transition were detected by quantitative real-time PCR (qPCR) in CD10high and CD10low OSCC cells. Mouse xenograft model and venous metastasis model were used to explore the potential regulatory mechanism of the resistance effect of CD10 on cisplatin. RESULTS: The higher expression of CD10 gene in different cell lines displayed enhanced cisplatin resistance ability. The expression of genes related to chemotherapy resistance, cell stemness, and the epithelial-mesenchymal transition was significantly higher in CD10high cells compared with CD10low cells. Moreover, the combination of cisplatin and Hh pathway inhibitors significantly reduced the resistance of CD10 to cisplatin in the xenograft model and venous metastasis models. CONCLUSION: CD10-positive cells are implicated in developing cisplatin resistance of OSCC, which could be related to its cancer stem cell characteristics regulated by the Hedgehog pathway.